Efficacy and safety of subcutaneous infliximab versus adalimumab, etanercept and intravenous infliximab in patients with rheumatoid arthritis: a systematic literature review and meta-analysis

Expert Rev Clin Immunol. 2021 Jan;17(1):85-99. doi: 10.1080/1744666X.2020.1858803. Epub 2020 Dec 28.


Objectives: There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

Methods: Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621).

Results: The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advantage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections, and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept.

Conclusion: CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.

Keywords: Adalimumab; CT-P13; biosimilar; etanercept; infliximab; rheumatoid arthritis.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adalimumab* / adverse effects
  • Adalimumab* / therapeutic use
  • Administration, Cutaneous
  • Administration, Intravenous
  • Antirheumatic Agents* / administration & dosage
  • Antirheumatic Agents* / adverse effects
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Biosimilar Pharmaceuticals* / administration & dosage
  • Biosimilar Pharmaceuticals* / adverse effects
  • Biosimilar Pharmaceuticals* / therapeutic use
  • Etanercept* / adverse effects
  • Etanercept* / therapeutic use
  • Humans
  • Infliximab / administration & dosage
  • Infliximab / adverse effects*
  • Infliximab / therapeutic use*
  • Treatment Outcome


  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • Infliximab
  • Adalimumab
  • Etanercept

Associated data

  • figshare/10.6084/m9.figshare.13490888.v1